Molnupiravir Use and 30-Day Hospitalizations or Death in Previously Uninfected Non-hospitalized High-risk Population with COVID-19

Butt et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiad195

Jun 2023

Retrospective 65,010 veterans in the USA, showing no significant difference in hospitalization/death with molnupiravir treatment. 1,729 patients received molnupiravir. Authors emulate a target trial closely matching the MOVe-OUT RCT and using 1,459 matched pairs.

Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer Chamod, Hadj Hassine, Huntsman, Marikawa, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Fountain-Jones, Kosakovsky Pond, Sanderson, twitter.com.

1. Chamod et al., Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage, Asian Medical Journal and Alternative Medicine, 23:3, asianmedjam.com/index.php/amjam/article/view/1448.asianmedjam.com.

2. Fountain-Jones et al., Effect of molnupiravir on SARS-CoV-2 evolution in immunocompromised patients: a retrospective observational study, The Lancet Microbe, doi:10.1016/S2666-5247(23)00393-2.sciencedirect.com, doi.org.

3. Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.mdpi.com, doi.org.

4. Huntsman, M., An assessment of the reproductive toxicity of the anti-COVID-19 drug molnupiravir using stem cell-based embryo models, Master's Thesis, scholarspace.manoa.hawaii.edu/items/cd11342c-b4dc-44c0-8b44-ce6e3369c40b.hawaii.edu.

5. Kosakovsky Pond et al., Anti-COVID drug accelerates viral evolution, Nature, doi:10.1038/d41586-023-03248-3.nature.com, doi.org.

6. Marikawa et al., An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations, Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475.sciencedirect.com, doi.org.

7. Sanderson et al., A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes, Nature, doi:10.1038/s41586-023-06649-6.nature.com, doi.org.

8. Swanstrom et al., Lethal mutagenesis as an antiviral strategy, Science, doi:10.1126/science.abn0048.science.org, doi.org.

9. twitter.com, twitter.com/LongDesertTrain/status/1597353291868155906.twitter.com/LongDesertTrain/status/1597353291868155906.

10. Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.wiley.com, doi.org.

11. Zhou et al., β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247.oup.com, doi.org.

12. Zibat et al., N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody, iScience, doi:10.1016/j.isci.2023.107786.sciencedirect.com, doi.org.

Important missing comments or errors? Let us know.

risk of death/hospitalization, 9.1% higher, RR 1.09, p = 0.75, treatment 48 of 1,459 (3.3%), control 44 of 1,459 (3.0%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Butt et al., 1 Jun 2023, retrospective, USA, peer-reviewed, 6 authors.

This Paper Molnupiravir All

Molnupiravir Use and 30-Day Hospitalizations or Death in a Previously Uninfected Nonhospitalized High-risk Population With COVID-19

MBBS Adeel A Butt, MS Peng Yan, MD Obaid S Shaikh, MD, MPH Saad B Omer, MD Florian B Mayr, PhD Victor B Talisa

The Journal of Infectious Diseases, doi:10.1093/infdis/jiad195

Background: Clinical benefit of Molnupiravir (MPV) in COVID-19 infected sub-populations is unclear. Methods: We used a matched cohort study design to determine the rate of hospitalization or death within 30 days of COVID-19 diagnosis among MPV treated and untreated controls.

Author Contributions Study concept and study design: Role of the Funding Source There was no funding source. Data Access Drs. Butt and Mr. Yan had complete access to the data at all times and accept responsibility for the integrity of this article.

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